{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:48:35Z","timestamp":1785149315405,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Liver fibrosis remains difficult to treat, in part because many hepatoprotective triterpenoids suffer from poor oral bioavailability and lack of optimized delivery formats. Ganoderma amboinense is a rare \u201cantler\u201d reishi species long valued in Eastern traditions yet scarcely studied for its phytochemical and pharmacological potential. Here, we report the first investigation of an ethanol-extracted G. amboinense sublingual dripping pill formulation (GDP) in a carbon-tetrachloride (CCl4)\u2013induced mouse model of liver fibrosis. Mice treated with GDP at one- and five-times the human equivalent dose were compared to groups receiving unprocessed G. amboinense powder (GP) or purified ganoderic acid A (GA-A). GDP significantly prevented CCl4-induced weight loss and hepatomegaly, normalizing liver-to-body weight ratios and serum AST\/ALT activities (p &lt; 0.05). Histological evaluation showed that GDP markedly reduced hepatocellular necrosis and collagen deposition, restoring tissue architecture. Furthermore, GDP suppressed hepatic expression of pro-inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2, COX-2) and profibrotic markers (TGF-\u03b21, CTGF, \u03b1-SMA) to levels comparable with or superior to GA-A. These results demonstrate that a dripping pill dosage form can effectively deliver G. amboinense triterpenoids and unlock their hepatoprotective activity, supporting further development of GDP as a novel liver-support nutraceutical.<\/jats:p>","DOI":"10.3390\/cimb47090697","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sublingual Dripping Pill Formulation of Ganoderma amboinense Fruiting Body Extract Attenuates CCl4-Induced Liver Fibrosis via Multi-Pathway Regulation"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2503-6063","authenticated-orcid":false,"given":"Chin-Feng","family":"Liu","sequence":"first","affiliation":[{"name":"Continuing Education Program of Food Biotechnology Applications, National Taitung University, Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-Ming","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taitung University, 369, Sec. 2, University Rd., Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-9465","authenticated-orcid":false,"given":"Chun-Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taitung University, 369, Sec. 2, University Rd., Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1007\/s00204-020-02885-1","article-title":"Drug induced liver injury: An update","volume":"94","author":"Stephens","year":"2020","journal-title":"Arch. 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